Sunday, 9 September 2012

Response on ENCODE reaction

The publication of ENCODE data raised substantial discussions. Clear, open, rational debate with access to data is the
cornerstone of science. For the scientific details the ENCODE papers are
totally open, and we have aimed for a high level of transparency e.g. a virtual
machine to provide complete access to data and code.

There is an important discussion
– which no doubt will continue throughout this decade – about the correspondence
between reproducible biochemical events on the genomes, their downstream cellular
and organismal functions, their selection patterns in evolution and their roles
in disease. ENCODE provides a substantial new dataset for this discussion, not
some definitive answer, and is part of a longer arc of science in this general
area. I touch on this on my blog

There are also
"meta" questions concerning the balance of "big" and
"small" science, and how "big" science projects should be conducted.
The Nature commentary I wrote focuses
on this.

ENCODE also had the
chance of making our results comprehensible to the general public: those who
fund the work (the taxpayers) and those who may benefit from these discoveries
in the future. To do this we needed to reach out to journalists and help them
create engaging stories for their
readers and viewers, not for the readers of Nature
or Science. For me, the driving
concern was to avoid over-hyping the medical applications, and to emphasize that
ENCODE is providing a foundational resource akin to the human genome.

With hindsight, we
could have used different terminology to convey the concepts, consequence and
massive extent of genomic events we observed. (Note to self: one can be precise
about definitions in paper or a scientific talk to scientists, but it’s far
harder via the medium of everyday press, even to the same audience). I do think
we got our point to the general public: that there is a staggering amount of
activity in the genome, and that this opens up a lot of sophisticated and highly
relevant scientific questions. There was a considerable amount of positive mainstream
press, sometimes quite nuanced. Hindsight is a cruel and wonderful thing, and
probably we could have achieved the same thing without generating this unneeded,
confusing discussion on what we meant and how we said it.

I am tremendously
proud of the way that the consortium worked together and created the resources
that it did. The real measure of a foundational resource such as ENCODE is not
the press reaction, nor the papers, but the use of its data by many scientists
in the future.

61 comments:

The ENCODE data will be an unparalleled resource for years to come - I don't think there's any doubt about that. I think the discussion of semantics among scientists is important, because our language is about conveying specifics, but I do hope that the articles in the popular press get people excited about science. Also, I'm betting that all this controversy will drum up some new ideas for how to analyze all the new data that's available.

Note to self: one can be precise about definitions in paper or a scientific talk to scientists, but it’s far harder via the medium of everyday press, even to the same audience.IMHO the issue is not the precission of ENCODE's definition of "function" but rather about the fact that ENCODE ignored the well established and defined concept of Junk DNA. It's as if some geographer would define hills with height over base > 100m as mountains. This would transform the majority of the world's surface into mountains. It is obvious that this wouldn't make sense even if the given definition is very precise.

The ENCODE Consortium is promoting the idea that the human genome is chock full of a vast network of regulatory sequences.

This flies in the face of abundant evidence that most of our genome is junk. Why do you ignore that evidence?

And why would humans need so much more regulatory DNA than, say Drosophila? or pufferfish? These are not trivial questions. You are challenging a model of gene regulation that has been built up over several decades.

Do you really think that the ENCODE data supplies such extraordinary evidence in support of such an extraordinary claim?

So much hinges on the operational definition of "functional". The historic notion of "junk" DNA includes DNA that is non-functional. A great deal is being written about what is an what isn't functional, and a great deal of it appears to be fundamentally divorced from reality with respect evolutionary science. At the grossest level, there exists a cost to adding a base, or a million bases to a genome, but that cost is so negligible that invoking it is little more than an advertisement of ignorance. For much of the rest that is being declared "functional", a similar argument is trivially deduced, and yet, proponents are advocating those very definitions. For example, the mere fact that DNA is transcribed to RNA in a tissue specific manner says NOTHING about function. A functioning knowledge of the mechanisms of transcriptional regulation, and of mutagenesis actually predicts that we will have useless transcription in a regulated manner. Ultimately, you seem to have promoted a definition of function that not only lacks a useful function, it is counter-productive.

You have T. Ryan Gregory complaining that function had already been known for years, yet on the other hand, complaining about the fact that a large amount of bio chemical function has been found. Which is it Gregory? Make up your mind! Of course what he refuses to admit, is that in the earlier years, the data that did indeed give hint to function, was largely ignored by the status quo, and now all those years of preaching the useless junk DNA paradigme to students and to the general public has now come back to bite them in the ass. Not to mention those all those sweet talking points given to ID theorist and creationist. No, we just couldn't have that! (Sarcasm emphasized)

As for Larry Moran challenging the findings of ENCODE. My question is, why cant he do this in peer review? If the counter evidence is there, as he insist it is, then he wouldn't even need funding. He could simply produce the data that already exist, but like Gregory, he chooses instead, to publicly ridicule and or marginalize the work of other very hard working researchers who have dedicated their precious time and effort into this project.

Again, it is easy to criticize from your a blog where your minions can shower you with praise and un-critical adulation. Do it the right way. Take it to the stage.

"You have T. Ryan Gregory complaining that function had already been known for years,"

"Function had already been known". Riight.

In what? In Junk DNA? In non-coding DNA? They were never the same thing. Most of your genome is still junk. TheMayan is going to distort T. Ryan Gregory's ideas, because themayan doesn't know squat about science. But it would be convenient if themayan were to quote T. Ryan Gregory in full, so that we can judge whether what Gregory wrote was accurate or inaccurate.

Creationists and IDers always quote-mine, so themayan's paraphrasing of Gregory is useless. Fork over the quote from Gregory himself.

Gregory correctly points out the guys who invented the Junk DNA hypothesis knew, way back in 1972, that much of it would be transcribed into RNA. They insisted though, that no organism-level function could constrain the DNA sequence of most of the human genome, and they were right.

The ENCODE consortium reported NO data indicating that most of the DNA sequence of the genome is constrained by an organism-level function. It's still junk.

TheMayan: "Of course what he refuses to admit, is that in the earlier years, the data that did indeed give hint to function, was largely ignored by the status quo..."

This is an old wives' tale; analogous to believing that your heart stops when you hiccup. Gregory disproved this false history by citing actual passages from scientists of the 70's and 80's.

Some dumb journalists and ID creationists write that "Junk DNA" inhibited research, but they have no evidence to back up. They refuse to even look at Gregory's citations.

ID creationists and dumb journalists need to make up a false history of science in order to get attention.

Birney: "For me, the driving concern was to avoid over-hyping the medical applications..."

Really? You mean like when you helped Nature produce a video cartoon in which ENCODE is presented as a mega-robot that destroys cancer and heart disease by punching it very hard?

Is that what you meant by avoiding over-hyping of medical applications? What, then, WOULD be hype by your definition? Immortality? Free nose jobs for ugly children? The ability to fly? What?

Birney: "With hindsight, we could have used different terminology to convey the concepts..."

True, you could have used accurate terminology.

Birney: "I do think we got our point to the general public: that there is a staggering amount of activity in the genome..."

No, no. You told the general public that there was 80% FUNCTION in the genome, FUNCTION not activity, and you told Ed Yong at Discover that would go to 100%. And almost all of the media interpreted function to mean "necessary", "needed", "essential". Was that accurate?

NPR reported John Stam as saying:

NPR: “Most of the human genome is out there mainly to control the genes,” said John Stamatoyannopoulis, a geneticist at the University of Washington School of Medicine, who also participated in the project.

Was John Stam telling the truth or lying, Ewan?

This is from the Independent:

The Independent: "Scientists have once and for all swept away any notion of “junk DNA” by showing that that the vast majority of the human genome does after all have a vital function by regulating the genes that build and maintain the body."

Does the vast majority of the human genome have a vital function by regulating the genes, Ewan?

This is from the New York Times:

NY Times: "As scientists delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered a complex system that controls genes. At least 80 percent of this DNA is active and needed."

Is 80% of human DNA active and needed, Ewan?

This is from the Washington Post:

Wash Post: "Indeed, the vast majority of human DNA seems to be involved in maintaining individuals’ well being — a view radically at odds with what biologists have thought for the past three decades"

Is the vast majority of human DNA involved in maintaining individuals’ well being, Ewan?

This is from USA Today:

USA Today: "International research teams have junked the notion of “junk” DNA, reporting that at least 80% of the human genetic blueprint contains gene switches, once thought useless, that control the genes that make us healthy or sick."

Is 80% of human DNA gene "switches" that control genes, Ewan?

Birney: "ENCODE also had the chance of making our results comprehensible to the general public..."

It's not complicated, Themayan. My complaint has three parts (and this isn't unique to ENCODE, it's so common as to be cliche in both the media and the primary literature).

First, there was never a time when non-coding DNA was *all* dismissed as "useless junk" such that functions were not considered. Quite the opposite -- functions were seriously considered for every new type of non-coding DNA when discovered. The early authors of the "junk DNA" concept explicitly mentioned possible functions for *some* non-coding DNA. Comings (1972) suggested 20% of the genome is actively used, for example.

Second, the concept of non-functional, non-coding DNA was not based on ignorance or giving up and just calling it "junk". There were (and still are) positive arguments for expecting much of the genome to be of little or no relevance to fitness. Mutational loads, variability in genome size, neutral evolution at the sequence level, 2/3 of the genome being transposable elements, etc. Several of these arguments have been around since the 1970s and they remain valid today.

Third, there is no evidence that a majority of the human genome is "functional" in any meaningful sense of that word. Of course some non-coding DNA is functional (regulatory regions, centromeres and telomeres, ribosomal RNA, etc.), but no one ever said otherwise. There are more examples coming up all the time, which is very interesting. But the total still hasn't even approached Comings's (1972) original figure of 20%. And even if some people are willing to interpret the current evidence as indicating that most DNA in the human genome will turn out to be functional, they still have to explain why a pufferfish does fine with only 1/10 as much whereas even the smallest salamander genome is 5x larger. This suggests that, even if 100% of the human genome is functional, a lot of eukaryotic DNA out there is not. That is, that the notion of non-functional, non-coding DNA remains valid. Claiming that humans are complex and so need more DNA is an expectation that was refuted in the 1950s. And, in any case, the human exceptionalism required to maintain the view that 100% functional in people but amount of non-coding DNA is irrelevant in pufferfishes and salamanders is biologically nonsensical.

The definition of "function" that is relevant to the Junk DNA hypothesis is this: DNA sequence constrained by organism-level function (not some parasitic-level function, like the biochemical functions of transposons copying themselves.)

The definition of "junk" that is relevant to the Junk DNA hypothesis is this: DNA sequence NOT constrained by organism-level function.

I have two questions.

1. Ewan, do you agree that the above definition of "function" vs. "junk" is the definition relevant to the Junk DNA hypothesis as it was put forward by, say, Ohno in 1973? Yes or no?

2. Ewan, by the above definition of "function"-- the definition relevant to the Junk DNA hypothesis-- what fraction of the genome is known for sure to be "functional" based on ENCODE's data?

cont.....Again you you accused me of quote mining even though you later agree with what I said, an yet you went on to quote mine Ohno. Here is what Ohno actually concluded….."INASMUCH as the only requirement to be qualified as partitioning sequences is to be untranscribable and/or untranslatable. it is not likely that these sequences came into being as a result of positive selection. Our view is that they are the remains of natures experiments which failed. The earth is strewn with fossils remains of extinct species, is it a wonder that our genome too is filled with the remains of extinct genes?"

A Brief History of the Status of Transposable Elements: From Junk DNA to Major Players in Evolution

In the 1970s, the field of population genetics was dominated by analysis of the genetic polymorphism of populations using allozymes, with the aim of deciphering population structuring (LEWONTIN 1974). The entire emphasis was on the role of point mutations in coding regions as the primary source of evolutionary change. Despite the observations ofMCCLINTOCK (1950) that in maize some genetic factors [e.g., the Activator (Ac)/Dissociator (Ds)] that can control the cell color of kernels were able to change their locations within and between chromosomes and could control the expression of some genes [see FEDOROFF (1994) for a biography of B. MCCLINTOCK], and the demonstrated presence of mobile DNA elements in bacteria (SHAPIRO 1969), the possibility that TEs could influence genetic polymorphism, and therefore genetic diversity, was, for the most part, ignored.

TRANSPOSABLE ELEMENTS AS PLAYERS IN EVOLUTIONExcept for their use as potential genetic tools, the interest in molecular analyses of TEs faded between 1990 and 2000, and the population approach was not really understood……

I find it very interesting that you accuse me of quote mining when I mentioned that one of Gregory's complaint was that function was already known, when even you confirm this by mentioning the citations that Gregory has posted on his cite. Secondly, the amount of papers Gregory cites on junk DNA compared to other types of genomic studies during that same time frame, are scant to say the least. Go to Gregory's website and see how few papers you find in published just during the 80's alone. I am old enough to remember the 70's and 80's, and I remember as students we were told time and time again, that only 2% of the genome was active and the rest was useless vestigial junk. We were told this in schools, books, science channels on television, and radio and science magazines. If function was known by scientist, (and I have no reason to doubt it), then it was one of the best kept secrets, and or again was ignored by the same status quo.

It seemed that for the status quo, the junk DNA paradigm was instead used as a poster child for bad design….E.g. Kenneth Miller, "Intelligent design cannot explain the presence of a nonfunctional pseudogene, unless it is willing to allow that the designer made serious errors, wasting millions of bases of DNA on a blueprint full of junk and scribbles. Evolution, however, can explain them easily"

Richard Dawkins, “The amount of DNA in organisms,” Dawkins wrote in 1976, “is more than is strictly necessary for building them: A large fraction of the DNA is never translated into protein. From the point of view of the individual organism this seems paradoxical. If the ‘purpose’ of DNA is to supervise the building of bodies, it is surprising to find a large quantity of DNA which does no such thing. Biologists are racking their brains trying to think what useful task this apparently surplus DNA is doing. But from the point of view of the selfish genes themselves, there is no paradox. The true ‘purpose’ of DNA is to survive, no more and no less. The simplest way to explain the surplus DNA is to suppose that it is a parasite, or at best a harmless but useless passenger, hitching a ride in the survival machines created by the other DNA.“

Diogenes says….."Some dumb journalists and ID creationists write that "Junk DNA" inhibited research, but they have no evidence to back up. They refuse to even look at Gregory's citations"

"ID creationists and dumb journalists need to make up a false history of science in order to get attention"

Prof. John Mattick, recently claimed that, ‘the failure to recognize the implications of the non-coding DNA will go down as the biggest mistake in the history of molecular biology’ [Genius of Junk (DNA), Catalyst, Thursday, 10 July 2003].

John Mattick is not a creationist or ID theorist.

JUNK DNAThe term is used mainly in popular science and in a colloquial way in scientific publications. "Scientific American" claims that its connotations may have slowed research into the biological functions of noncoding DNA.[32] Source Wikipedia and Scientific American, & I know neither to be creationist cites or orgs.

It may very well be that your undergraduate instructors told you that junk DNA was all useless. It does not follow that researchers working on non-coding DNA dismissed the idea of function. That is what I have tried to show -- they published ideas on potential function all the time in the primary literature throughout the 1970s and 1980s. Every new type of non-coding DNA that was discovered (satellite DNA, LINEs, SINEs, ERVs, introns, and pseudogenes) had functions considered from the outset.

It also does not follow from whaty you heard in class or what you saw in Scientific American that the authors of the original junk DNA papers argued that all non-coding DNA is useless. Read Comings (1972), which is the first detailed treatment of the topic. Moreover, both the junk DNA and selfish DNA papers were met with strong resistance -- the prevailing view was that most genomic DNA must have a function or else it would have been deleted.

Ohno's version of "junk DNA" referred to pseudogenes, which is the context for the line you quoted. He did acknowledge non-sequence specific functions such as spacing among genes.

Of course, all of this is secondary to the fact that the ENCODE results do not, in fact, suggest anything like 80% "functional" non-coding DNA in the human genome under any biologically meaningful definition.

I am old enough to remember the 70's and 80's, and I remember as students we were told time and time again, that only 2% of the genome was active and the rest was useless vestigial junk. We were told this in schools, books, science channels on television, and radio and science magazines.

If that were true, then why do you have NO DOCUMENTARY EVIDENCE for your 2% number, not one citation in the peer-reviewed scientific literature asserting your 2% number-- and why do you ignore the huge amount of contrary evidence amassed and fully cited by Gregory?

Ryan Gregory cited Comings (1972) as writing the following:

Comings, 1972: These considerations suggest that up to 20% of the genome is actively used and the remaining 80+% is junk. But being junk doesn’t mean it is entirely useless. Common sense suggests that anything that is completely useless would be discarded. There are several possible functions for junk DNA...

Then Comings lists some functions for junk DNA.

Comings said 20% functional. Let's compare his prediction to the results of ENCODE.

Ewan Birney wrote: "However, on the other end of the scale – using very strict, classical definitions of “functional”... such as a transcription factor binding site to the actual bases – we see a cumulative occupation of 8% of the genome. With the exons... that number goes up to 9%...

I am old enough to remember the 80's, and I was never told any such thing about 2% of the genome being functional.

If your teachers told you that only 2% of the genome was functional, then it is your terrible school's fault for contradicting the scientific literature. That is your school's problem-- but you are blaming Ohno, Comings, Crick, Doolittle, Ohta et al.! Where is your documentary evidence?

Why are you ignoring Gregory's citations? Why do you ignore Birney's estimate that only 20%, at most (very optimistically), of your genome is functional. Why do you ignore the scientific evidence?

Prof. John Mattick, recently claimed that, ‘the failure to recognize the implications of the non-coding DNA will go down as the biggest mistake in the history of molecular biology’ [Genius of Junk (DNA), Catalyst, Thursday, 10 July 2003].

I cannot judge Mattick's meaning in context, because I don't have the original. It is universally true that creationists take quotes out of context, sifting through vast piles of literature to find one quote with a different meaning out of context than its original meaning. Thus, I cannot fully disagree with Mattick's meaning in context.

However, Mattick's quote, at least its apparent meaning taken out of context, is obviously dead wrong, and contradicted by the history of the last 50 years of research in molecular biology, which has been largely focused on finding functions in non-coding DNA.

Nobel Prize for Jack Szostak and co-workers in 2009, for research in 1980’s on function in non-coding DNA (telomeres).

The structure of tRNA was known by 1964, crystal structure solved in 1974. tRNA is made from non-coding RNA.

The ribosome was known to be largely nucleic acid in the 1950's, general molecular structure known since the early 1970s, by the 1980's it was known the ribosome was a ribozyme-- based on functions residing in non-coding DNA.

Explain to me how scientists did not pay enough attention to function in non-coding DNA?

Is there a single base pair of non-coding DNA that had a novel function discovered by any creationist or ID proponent-- any? Even one base pair? No. Not one.

"Scientific American" claims that its connotations may have slowed research into the biological functions of noncoding DNA.[32] Source Wikipedia.

Thanks for citing me. I wrote that sentence in the Wikipedia entry. Since you trust as reliable the sentences I wrote in Wikipedia, why am I unreliable when I say most of your genome is still junk?

Since you trust Scientific American as a reliable source (I DO NOT), maybe you'd like to read this debunking of the ENCODE hype at Scientific American:

Scientific American: "A similar kind of 'theory of everything' hype surrounded the [Human Genome Project] but in the case of the [ENCODE Project] the hype has been ratcheted several fold... And science journalists who should know better (in Science, BBC, NY Times, The Guardian, Discover Magazine) made things worse by conflating junk, non-protein-coding and regulatory DNA...

So even bona fide junk DNA is not neutral and is still subject to evolutionary scrutiny – but neither does every single element map to a specific function. We know this partly because genome size varies very widely across species whereas the coding capacity is much less variable (the “C-value paradox”), partly because removal of some of these regions does not affect viability in several animal models, including mice. It’s this point that [the ENCODE Project] almost deliberately obfuscated by trumpeting (or letting be trumpeted) that 'junk DNA has been debunked', ushering in 'a view at odds with what biologists have thought for the past three decades.' ...The EP results are important and will be very useful – but they’re not paradigm shifters... and should not pretend to be."

I have already spoken about issue of what scientist knew and what we as students were taught, and which in many cases is still being taught. A couple of weeks ago I gave you an example of PZ Myers in a room full of biology majors who said many things including ridiculing those who claim the genome contains massive amounts of information, and then goes on to insinuate that those who are trying to associate function within non protein coding regions of DNA, are simply biologist who are looking for job security. Why is there no anger on your part towards guys like this. How can you build interest among young people by ridiculing those who are trying to advance science? ‪Rummaging About in the Genetic Junkyard Skepticon 4 PZ Myers‬http://www.youtube.com/watch?v=DRsN7w7iW08

This is why ignoring is a type of ignorance in itself, and how it can, and has slowed down scientific progress, and let me just use one more example below.Everyone knows of the Barbara Mcclintock story and how junk DNA was ignored long before the term "junk DNA" even existed.Yes, Mcclintock was a respected science of her day, this is true, but what is also true, is that her specific work on maze and transposable genetic elements was largely ignored, only to later be redeemed in 1983 decades after her initial work. Think of all those decades lost when we could have been researching instead of condemning others because their finding did not fit or conform to our own personal world views or biases. Yes that right, even scientist can have and be bias. And again it would be pretty embarrassing to finally admit after all these years that maybe the word junk should not be used anymore in light of histories lessons. Maybe the term 'no known function' would be a safer and more accurate term. However here below is my response to yours. "Surely you jest"No sir. Not in this case."Where it is said that she defiantly and deliberately challenged the paradigme view of the gene"Barbara McClintock: Pioneering Geneticist (Unlocking the Secrets of Science) [Library Binding]Kathleen Tracy (Author)From all her experiments with maize (Indian corn), Barbara discovered that there were movable elements inside each gene, which she called "transposable elements." Because her revolutionary ideas challenged a cemented belief among mainstream geneticists that genes were fixed in place, her research was rejected. She was deeply stunned and bitterly disappointed at the close-mindedness of the scientific community.

Digital Archives Cold Spring Harborhttp://library.cshl.edu/sp/scientists/barbara_mcclintock/mcclintock_biography.htmlMcClintock's studies and observations of mutation in kernels of maize (corn), led to her discovery of transposable genetic elements. Although the scientific community largely ignored her concepts, advances in molecular and microbial genetics ultimately proved her findings correct. She is now credited as the discoverer of transposable—or “jumping”—genes, a discovery which is at the very root of much of today's research in genetic engineering.

http://en.citizendium.org/wiki/Barbara_McClintockHer work on controlling elements and gene regulation was conceptually difficult and was not immediately understood or accepted by her contemporaries; she described the reception of her research as "puzzlement, even hostility".[7] Nevertheless, McClintock continued to develop her ideas on controlling elements. She published a paper inGenetics in 1953 where she presented all her statistical data and undertook lecture tours to universities throughout the 1950s to speak about her work. She continued to investigate the problem and identified a new element that she called Suppressor-mutator (Spm), which, although similar to Ac/Ds displays more complex behavior. Based on the reactions of other scientists to her work, McClintock felt she risked alienating the scientific mainstream, and from 1953 stopped publishing accounts of her research on controlling elements.

As for Diogenes.....Your initial complaint was.."Some dumb journalists and ID creationists write that "Junk DNA" inhibited research, but they have no evidence to back up"

After I cite a couple of sources to back up my claim including Wikipedia.You then respond by saying..... "Thanks for citing me. I wrote that sentence in the Wikipedia entry"

Diogenes, are you a dumb journalist or creationist? Otherwise you statement makes little sense.

You then go on to ask me why I questioned your credibility?....

"Since you trust as reliable the sentences I wrote in Wikipedia, why am I unreliable when I say most of your genome is still junk?"

I'm not even sure how to respond to this example of a blatant contradiction. And by the way, Wiki articles require sources other wise they are rejected or in other cases, they are published, but with a 'citation needed caveat'

As for Matick's statement ‘the failure to recognize the implications of the non-coding DNA will go down as the biggest mistake in the history of molecular biology’

Nowhere did he say that there wasn't any past research going on concerning this subject. Again his point was sciences failure to recognize the implications of the non-coding DNA" as in the status quo. As he is also a member of the science community, and did not exclude himself as a member, I can only assume that he may also be partly to blame, but this particular point is moot.

One more example, and these are not my words below but the words of favorite of mine, and I'm sure yours too, J. Wells, and all kidding aside, before you attack the messenger, consider the substance as it relates to what I said before.

In 1980, W. Ford Doolittle and Carmen Sapienza wrote in Nature (284:601) that many organisms contain "DNAs whose only 'function' is survival within genomes," and that "the search for other explanations may prove, if not intellectually sterile, ultimately futile." In the same issue of Nature(284:604), Leslie Orgel and Francis Crick wrote that "much DNA in higher organisms is little better than junk," and its accumulation in the course of evolution "can be compared to the spread of a not-too-harmful parasite within its host." Since it is unlikely that such DNA has a function, Orgel and Crick concluded, "it would be folly in such cases to hunt obsessively for one."

Dawkins continued to rely on junk DNA in his 2009 book The Greatest Show on Earth: The Evidence for Evolution. "It is a remarkable fact," he wrote, "that the greater part (95 per cent in the case of humans) of the genome might as well not be there, for all the difference it makes." In particular, pseudogenes "are genes that once did something useful but have now been sidelined and are never transcribed or translated." Dawkins concluded: "What pseudogenes are useful for is embarrassing creationists. It stretches even their creative ingenuity to make up a convincing reason why an intelligent designer should have created a pseudogene... unless he was deliberately setting out to fool us."

But if most of our DNA is functional, as the ENCODE results suggest, then the "junk DNA" argument against ID collapses.So the four bloggers listed above are doing everything they can to discredit the ENCODE project's estimate of functional DNA. Yet whatever the estimate may currently be, it is certain to increase with further research. In 2007, the ENCODE pilot project reported on the basis of about 200 datasets that our DNA is "pervasively transcribed," suggesting functionality. The 2012 results, based on 1,640 datasets, documented that "the vast majority (80.4%) of the human genome" is biochemically functional in at least one cell type. But ENCODE has so far sampled only a fraction of the cell types in the human body.Clearly, we have a lot more to learn about our genome -- but not if we start by assuming that most of it is junk.

@TheMayan: But if most of our DNA is functional, as the ENCODE results suggest

What nonsense! Multiple ENCODE scientists admitted that their results do not debunk the Junk DNA hypothesis, and they've shown that only a small fraction of the genome is functional.

Just the other day, ENCODE researcher Max Libbrecht wrote:

"Max Libbrecht from ENCODE and the ENCODE AMA on reddit here... I thought I'd put in that I essentially agree with this article: ENCODE did not debunk the idea of "junk" DNA, contrary to many news outlets. Here is one summary of the true results and their misinterpretation -- there are many others:http://selab.janelia.org/people/eddys/blog/?p=683" [Source: Mike White's blog]

Max above approvingly cited a blog post by Cryptogenomicon, which is a devastating smackdown of the hype regarding the "Death of Junk DNA." Read Cryptogenomicon before you comment again.

Ewan Birney wrote on this very blog: "...using very strict, classical definitions of “functional”...we see a cumulative occupation of 8% of the genome. With the exons... that number goes up to 9%."

Eisen: "So it is more than just intellectually lazy to start the story of ENCODE this way. It is dishonest – nobody can credibly claim this to be a finding of ENCODE. ...And yet, each of the dozens of news stories I read on this topic parroted this absurd talking point – falsely crediting ENCODE with overturning an idea that didn’t need to be overturned. ...The pullquote from the [ENCODE] press release is that the human genome is a “massive control panel with millions of switches regulating the activity of our genes”. ...But as even the authors admit, only some fraction of these sequence will actually turn out to be involved in gene regulation. So it is simply false to claim that the papers have identified millions of switches." [Michael Eisen's blog]

I listed quotes from many other ENCODE scientists admitting that they did not disprove the Junk DNA hypothesis at Mike White's blog.

TheMayan: "But if most of our DNA is functional, as the ENCODE results suggest, then the "junk DNA" argument against ID collapses."

On the contrary, the existence of just one viral DNA insertion (8% of the genome) or transposon (about a million of those, 45% of the genome) demolishes Intelligent Design.

I think you are missing the point of the quotes from the selfish DNA papers. You also seem to miss the point of the papers as well, and what it implies about the state of assumptions regarding non-coding DNA in the early 1980s.

As to the first, the important points are that we should not "hunt obsessively" for functions at the organism level if there is a plausible explanation at the subgenomic level (i.e., that the element is parasitic). Not, "we should never consider function". That "we should not keep looking for function after function after function in a sequence, assuming that there absolutely must be one."

Read the rest of the papers. Especially parts like this:

"It would be surprising if the host genome did not occasionally find some use for particular selfish DNA sequences, especially if there were many different sequences widely distributed over the chromosomes. One obvious use … would be for control purposes at one level or another."

Two things need to be understood about these papers. One, they were written in response to the prevailing tendency to "look obsessively for function". This was the genomic counterpart to Gould and Lewontin (1979) about adaptationism in studying morphological and behavioural traits. If this were not the prevailing assumption, then these two papers would not have been necessary -- let alone published in Nature.

In 2007, the ENCODE pilot project reported on the basis of about 200 datasets that our DNA is "pervasively transcribed," suggesting functionality. The 2012 results, based on 1,640 datasets, documented that "the vast majority (80.4%) of the human genome" is biochemically functional in at least one cell type.

What nonsense! The fact 76% of the genome is transcribed into RNA, often at very low levels, has nothing to do with the Junk DNA hypothesis. Now ID has a problem with junk RNA on top of your massive problem with junk DNA. No intelligently designed system would have 76% transcription when most of that RNA just gets degraded.

David Comings, in the FIRST published use of the term 'junk DNA', wrote:

Comings, 1972: "The observation that up to 25% of the genome of fetal mice is transcribed into rapidly labeled RNA, despite the fact that probably less than half this much of the genome serves a useful function, indicates that much of the junk DNA must be transcribed... There are several possible reasons why it is transcribed..."

Comings then goes on to list several potential functions for Junk DNA.

So Comings in 1972 wrote "much of the junk DNA must be transcribed."

You, TheMayan, in 2012 write: 'our DNA is "pervasively transcribed,"' and on this basis, you claim Junk DNA is disproven.

No, this confirms Comings' statement in 1972 that "much of the junk DNA must be transcribed."

Do you understand how you know nothing, nothing, about genetics or about the Junk DNA hypothesis, and have failed at basic logic?

Yes, YOU are delusional and Psychotic as evident in your continual berating comments here and elsewhere. Also, where is the blog you promised on how Shapiro is "Scared to death of you"? What a joke!! And I never said anything about ID, Creationism or Christianity, another delusional projection from you.

Now that's a fair question. True, I've been a bit lax posting at my blog. I have a big post I'm working on about ENCODE, and I hope to post tonight or tomorrow. Then I'll go after Shapiro. That might not be till next week.

Do you see when Max Libbrecht of ENCODE showed up at Mike White's blog to say the critics are right-- ENCODE didn't disprove Junk DNA?

Perhaps you are a bit lax because you are too busy at the Christian post telling people you are a theist to prop up your arguments. Also, whether ENCODE disproved Junk DNA or not is a matter of opinion. I will say this however, it's not looking too good for the Junk DNA groupies..

Diogenes, the only reason why I'm responding to your many assortments of selected quote mining for the simple reason that I feel inaccuracies must be challenged and cited. First off lets start with this your 'Encode says what?' citation.

The first clue should have been the first line.....

"So I read in the newspaper this week that the ENCODE project has disproven the idea of junk DNA. I sure wish I’d gotten the memo, because this week a collaboration of labs led by myself, Arian Smit, and Jerzy Jurka just released a new data resource that annotates nearly 50% of the human genome as transposable element-derived, and transposon-derived repetitive sequence is the poster child for what we colloquially call “junk DNA”.

He is speaking of the popular press as in "newspaper" and He cited newspapers and not ENCODE's own release (and this is important to take note of) Secondly when he mentions that his lab just released study on 50% of the human genome being transposable element, etc. He is using the term junk DNA in its "colloquial" sense which can simply means ncDNA and not necessarily useless junk. As many already know, important function has been found in transposons.

Again Barbera Mcclintock whose work was ignored for decades until she was finally redeemed decades later was the first to discover these elements, but I digress.

He goes on to say..."The newspapers went on to say that ENCODE has revolutionized our understanding of noncoding DNA by showing that far from being junk, noncoding DNA contains lots of genetic regulatory switches. Well, that’s also odd, because another part of my lab is (like a lot of other labs in biology these days) studying the regulation of genes in a model animal’s brain (the fruit fly Drosophila). We and everyone else in biology have known for fifty years that genes are controlled by regulatory elements in noncoding DNA. (Well, I’ve only known for thirty years, not fifty, I admit — only since Mrs. Dell’Antonio kicked me out of high school biology class and gave me a molecular genetics textbook to read by myself."

Here again, he is speaking of the newspapers release but doesn't cite fault for reason you insisted, his problem seems to be with reporting that this is something new, when he goes on to say we have known this for fifty years.

He continues and says......"Now, with all respect to my journalist friends, I’ve learned not to believe everything I read in the newspapers. I figured I’d better read the actual ENCODE papers. This is going to take a while. I’ve only read the main Nature paper carefully so far (there’s 30+ of them, apparently, across multiple journals). But it’s already clear that at least the main ENCODE paper doesn’t say anything like what the newspapers say"

Yes this is the wise thing to do. Read the actual data.I'm not going to go into everything he says other than he raises some questions, but thats what scientist are supposed to do, and when he speaks of that actual ENCODE release this is as critical as he gets.....

"ENCODE calls a piece of DNA “functional” if it reproducibly binds to a DNA-binding protein, is reproducibly marked by a specific chromatin modification, or if it is transcribed. OK. That’s a fine, measurable operational definition. (One might wonder, why not just call “DNA replication” a function too, and define 100% of the genome as biochemically functional, but of course, as Ewan Birney (the ENCODE czar) would tell you, I would never be that petty. No sir.) I am quite impressed by the care that the ENCODE team has taken to define “reproducibility”, and to process their datasets systematically"

Diogenes Let me point one other thing out concerning selected quote mining tactics.

Example... Eisen: So it is more than just intellectually lazy to start the story of ENCODE this way. It is dishonest – nobody can credibly claim this to be a finding of ENCODE. ...And yet, each of the dozens of news stories I read on this topic parroted this absurd talking point – falsely crediting ENCODE with overturning an idea that didn’t need to be overturned. ...The pullquote from the [ENCODE] press release is that the human genome is a “massive control panel with millions of switches regulating the activity of our genes”.

This is how Larry Moran puts it concerning Eisen...."Here's the interesting thing. Many of us are upset about the press releases and the PR because we don't think the ENCODE data disproves junk DNA. Michael Eisen's perspective is entirely different. He's upset because, according to him, junk DNA was discredited years ago" "Eisen is wrong, junk DNA is alive and well. In fact almost 90% of our genome is junk"

Besides criticizing quote mining tactics, the bigger point I'm making, is that even seasoned scientist and scholars are getting confused and stumbling over who said what, and what does junk really mean? Again, I say in response to ENCODES eulogy, not just rest in peace, but good riddance to this outdated paradigme. When speaking of parts of the genome we dont yet fully understand, lets be wiser and learn our lesson from history and replace this term, and instead use the term 'no known function'

Gregory, as I said before, although I disagree with many of your assessments, and your portrayal of past historic events within there full context. I do respect your contributions to science, and I think its only fair to tell you that one of the reasons I posted that last response, was because you were one of the names mentioned in the article. You can read full article at...

http://www.evolutionnews.org/2012/09/why_all_the_fus_1064721.html

I'm also curious to know if you watched the PZ Myers lecture I cited, and if you did, do you agree with his presentation?

Thank you for the kind comments. I think we may be talking about two different aspects of past history. There may have been a period where people were often taught that non-coding DNA is all useless. It may have been a common view in the media. I haven't looked into this side of things in detail, as it's much more difficult to quantify. (I did, however, have an assistant go through genetics textbooks back 30 years at one time, so I could look into that info again sometime).

What I am talking about is what was actually being said in the primary literature. In that case, it is abundantly clear that there was no widespread dismissal of possible functions for non-coding DNA among the researchers working in the field. I have not been quoting selectively, either -- I looked at the papers that first described each type of non-coding DNA elements, for example, or review papers from the period, or news stories in Science and Nature from that time. All of them show that function was a common expectation, or at least a serious question, throughout the supposed period of dismissal.

If your profs got it wrong, that's a shame. If the media got it wrong, that's not so surprising. Same thing still happens all the time -- see, e.g., ENCODE.

In terms of PZ Myers, or ID proponents, I personally don't think non-functional junk DNA is all that relevant to the fight from either side. Why should "intelligent design" assume that nothing is non-functional? Our own intelligently designed artifacts often have crap in them. Who would argue that the computer code for Windows is flawless and without non-functional, redundant, sloppy, or otherwise unnecessary bits? I have never seen a clear articulation of the reason that ID predicts no non-functional DNA (other than the obvious "God don't make no junk" -- and even then, why not?).

Well then Dr Gregory let me try to make this more clear. Maybe its my fault in failing to comunicate properly. The question doesn't seem to be that scientist didn't have a clue that we would someday find function.This point is moot. The question is the amount of function, and the sheer complexity that the human genome project first revealed and how ENCODE is trying to decode this vast amount information. I have heard some scientist say that the amount of data left people with their jaws dropping from the initial sequencing alone.

As I said before, if you read Matticks statement, he is not necessarily denying that there was zero research or interest. In my opinion he is referring to sciences failure to recognize the full importance of junk DNA. There are many scientist today who have said and are still saying that much of what we have discovered was once thought to be useless junk DNA, but this is not necessarily an either or black or white argument. Both our assessment can be true at the same time.

Again, it is the amount of data that was unexpected, i.e. the amount of junk DNA that turned out not to be useless junk after all. They cant all be wrong. Francis Collins and many others including some I already cited have also said the same, and this is not just a matter of un-enlightened teachers or popular science magazines. As I said before, very influential scientist like Dawkins, Miller and many others tried for many years to use junk DNA as a poster child for bad design and spoke of how useless junk was better predicted by the neo Darwinian model.

As for ID, I'm not sure this is the proper forum to get into a debate concerning intelligent design, but on another forum, if you have the time, sure why not? The real point concerning the questioned I asked about PZ Myers, was a very specific one. It had to do with the specific lecture I cited, and the question was, if you agreed with his presentation? Do you think it is appropriate to down play the role of ncDNA and tell students, those who are looking for function are only doing it for job security? How can telling these young future scientist to not concern themselves with researching possible function, or publicly ridiculing and trying to humiliate those that do, a good thing? Its a fair question. I'm not really sure If I can make my concerns anymore clear.

Mattick is wrong about the state of research on the topic at that time. I'm not sure how else *I* can make *my* point any clearer.

I am not sure I have seen PZ Myers's lecture. He's not a genome biologist, and he is predominantly focused on atheism and defending evolution from creationists, so I don't know that I would consider that a definitive source for information on genomic research.

Cryptogenomicon says that scientists have know for a long time that there is function in NON-CODING DNA. What do you think that means? Do you think that means that scientists have know for a long time that there is function in Junk DNA? If that's what you think.... sheesh.

@TheMayan: "He is using the term junk DNA in its "colloquial" sense which can simply means ncDNA and not necessarily useless junk."

NO. Cryptogenomicon says:

Cryptogenomicon: "The “junk DNA” question is about how much DNA has essentially no direct impact on the organism’s phenotype – roughly, what DNA could I remove (if I had the technology) and still get the same organism.”

That is certainly not non-coding DNA!

There is no way anyone can really interpret that to mean non-coding DNA = Junk, the way you do.

You say: "He is using the term junk DNA in its "colloquial" sense which can simply means ncDNA and not necessarily useless junk."

NO. Cryptogenomicon says:

"There’s likely to be other nonfunctional DNA “junk” too..."

How, how could he be more clear?

He says "nonfunctional DNA junk". But you say that he "simply means ncDNA and not necessarily useless junk."

Do you think "useless" is different from "nonfunctional"? Or what, what, are you going on about?

Why are you so selectively quoting from Cryptogenomicon? You must be very selective indeed to tiptoe around his unambiguous statements.

Here is what Cryptogenomicon says:

"The human genome has a lot of junk DNA... the genome is mostly nonfunctional...

...the main ENCODE paper cites neither Orgel/Crick [1980] or Sapienza/Doolittle [1980]; what this means is, regardless of what we read in the newspapers, ENCODE is not actually trying to interpret their data in light of the current thinking about junk DNA...

...most reasonable people (ok, I) would say at this point that the human genome is mostly junk...

...The newspapers add, “therefore it’s not junk”, but that’s a critically incorrect logical leap... But as far as questions of “junk DNA” are concerned, ENCODE’s definition isn’t relevant at all."

Why do you not mention those unambiguous statements?

He defines "Junk" quite precisely and it's NOT non-coding DNA as you claim!

Again, this is the article that Max Libbrecht of ENCODE cited approvingly three times-- twice at Reddit, once at Mike White's blog.

@TheMayan: "He [Cryptogenomicon] is using the term junk DNA in its "colloquial" sense which can simply means ncDNA and not necessarily useless junk. As many already know, important function has been found in transposons."

I am tired of dishonest ID creationists using innuendo and insinuation to IMPLY that most nucleotides in most transposons have been shown to be functional.

To the extent that your sentence has meaning, it is a lie-- although to be fair, you are using vague waffle words, to just insinuate that most nucleotides in most transposons have been shown to be functional.

If you actually came out and really said that, then you would be a liar. But admittedly, you don't say that outright. You say:

@TheMayan: "As many already know, important function has been found in transposons."

Like all ID creationists, you write sentences without articles or quantities or numbers in front of the nouns. Thus your sentence says "function has been found", with no articles or quantities or numbers in front of the noun "function." Thus you insinuate without saying that most nucleotides in most transposons have been shown to be functional.

Cunning. This is a very common ID creationist writing style, to deceive by insinuation, without outright lying. It's practiced; ID creationists are drilled on it.

There are million transposons. They make up 45 percent of your genome, about 1.4 BILLION nucleotides. The experiments you cite show that 10 nucleotides, and 10 nucleotides there, have been co-opted as regulatory elements to control genes.

A few transposon genes are used at the organismic level-- less than a dozen out of one million transposons.

So if we count by nucleotides within transposons, only a fraction of a fraction of all nucleotides within transposons have been shown to be functional.

But you use insinuation to claim them all for "function"! Cunning. You have learned from Jonathan Wells and Casey Luskin, all right.

They don't contradict. It was a misunderstanding, later resolved. They are in agreement about Junk DNA.

Michael Eisen wrote a post in which he said that newspapers claim ENCODE just proved non-coding DNA has a function. But Eisen objected, basically saying that scientists already knew non-coding DNA had a function.

Your quote from Larry comes from that first post: "Here's the interesting thing. Many of us are upset about the press releases and the PR because we don't think the ENCODE data disproves junk DNA. Michael Eisen's perspective is entirely different. He's upset because, according to him, junk DNA was discredited years ago"

Moran was wrong in interpreting Eisen's point. Eisen meant that scientists have always known non-coding DNA can have function, but Moran thought he meant there is no Junk DNA.

This confusion was cleared up shortly thereafter. Eisen later wrote another post where he expressed himself clearly.

Eisen: "Given that such a large fraction of the genome is biochemically active... it is simply impossible for such a large number of molecular traits to have been driven to fixation by selection – argues strongly that most biochemical events do not contribute significantly to fitness... ... it is all but impossible that we would still exist if every new molecular event had a strong phenotypic effect.

This, of course, does not mean that all these molecular events do nothing... But we are generally interested in different types of function – things that did arise through natural selection, are maintained by purifying selection, and whose disruption will cause a disease or other significant phenotype... here, I think we should once again take our cue from Kimura... meaning that adaptive change had to be demonstrated, not assumed. We need to apply the same logic to molecular interactions." [Source]

"There are many scientist today who have said and are still saying that much of what we have discovered was once thought to be useless junk DNA"

No, not many; a few scientists, but many journalists.

And, as Gregory would tell you, neither the journalists nor the scientists who say "Long dismissed as junk..." ever have citations to old-times scientists saying (for example) that regulatory elements were all junk, or that all non-coding DNA were junk, etc.

In the phrase "Long dismissed as junk..." the verb is in passive tense. Passive tense verbs allow the speaker to NOT identify who, precisely, did the dismissing. Who dismissed all non-coding DNA as junk? Who dismissed regulatory elements as junk, or RNA genes as junk?

If you say "Long dismissed as junk..." the passive tense verb absolves you of the responsibility to cite a source that did the dismissing.

If you used an active tense verb, you would have to name names and give citations. "Prof. Smith dismissed non-coding DNA as junk..." No, if you said that, Prof. Smith would object.

What is your take on Creation activists? As for me posting your real name, why bother, because of course you will deny it, but we both know who you are on CP, you are the one whom calls people *liars* on a regular basis. Hey, perhaps if you post as Igor or L Moreau no one will notice..

Why didn't you answer my question on what your take is on 'Creation Activists'?

And yeah, I'm not revealing your real name because of course you will lie and say it isn't you, just like Igor and L Moreau are not you. You're a joke and fortunately a no body in the world of Science, except a Larry Moran groupie kicking and screaming on a sinking ship.

BTW, you never called me a liar on CP, but you do on a regular basis with many other people there, not to mention here, reddit, Larry's blog (there you did call me a liar), HP blogs and the list goes on and on.

Hey, why don't go back to UD and finish what you started, oh yeah,, you ran off with your tail between your legs after you made a complete ass of yourself.

Misc, if you do not start spelling your ad hominems correctly, you will loose this debate as you always loose.

Misc asserts that I comment at Christian Post under my "real name" which he will not reveal to me, because if I knew my real name, I might, I don't know, get superpowers or something. He's vague on why he won't tell me my "real name." At Christian Post, of all places.

Misc: Hey Igor, I mean L Moreau, I mean, Diogenes...

And yeah, I'm not revealing your real name because of course you will lie and say it isn't you, just like Igor and L Moreau are not you.

What other names do you call me by? Genghis Khan? Cthulhu? Pazuzu? Voldemort?

When you hear a voice at night telling you you're worthless, do you think that's me too?

Wikipedia: The Fregoli delusion, or the delusion of doubles, is a rare disorder in which a person holds a delusional belief that different people are in fact a single person who changes appearance or is in disguise. The syndrome may be related to a brain lesion and is often of a paranoid nature with the delusional person believing themselves persecuted by the person they believe is in disguise.

Does it comfort you to believe that when you are made to look foolish everywhere on the internet, there's only one person behind that?

I suppose it is comforting believing that only one person is vastly smarter than you. Alas, the truth is that there are many.

Nope, just Igor and L Morea as you were too chicken to face Shapiro on his confrontation about you, and you kept whining all over the place he banned you, which he did not. BTW, he just did a similar assessment on your ideology zealot friend Kwok, wonder why he wasn't 'banned'

To put my suspicions to rest about CP, why don't you tell me your first name? This person's communication style is strikingly similar to yours, such as calling people liars left and right, using the phrase 'Waaaaahhhh' and an over the top hate for ID, to name a few.

So go ahead, set the record straight and can check around to see if your telling the truth...

About Ewan Birney

Professor Birney is joint Director of EMBL-EBI with Rolf Apweiler, and runs a small research group.

Professor Birney played a vital role in annotating the genome sequences of the human, mouse, chicken and several other organisms; this work has had a profound impact on our understanding of genomic biology. He led the analysis group for the ENCODE project, which is defining functional elements in the human genome. Ewan’s main areas of research include functional genomics, assembly algorithms, statistical methods to analyse genomic information (in particular information associated with individual differences) and compression of sequence information.

Birney completed his PhD at the Wellcome Trust Sanger Institute with Richard Durbin, and worked in the laboratories of leading scientists Adrian Krainer, Toby Gibson and Iain Campbell. He has received a number of prestigious awards including the 2003 Francis Crick Award from the Royal Society, the 2005 Overton Prize from the International Society for Computational Biology and the 2005 Benjamin Franklin Award for contributions in Open Source Bioinformatics. Ewan was elected a Fellow of the Royal Society in 2014, and a Fellow of the Academy of Medical Sciences in 2015.